Thomas J. Waldschmidt, PhD
Research Laboratory
Contact Information
Phone: 319-335-8255
1035 Medical Laboratories
B lymphocytes in health and disease: The Waldschmidt
laboratory is focused on the studying the function of B cells, one of
the key lymphocyte subsets within the adaptive immune system. B cells
produce antibodies, an essential weapon used by the body to eliminate
extracellular pathogens like bacteria and fungi. Antibodies induced by
vaccines are also crucial to protect against infection with viruses such
as influenza. Work in the laboratory is focused on three facets of B
cell biology: The first is to understand the development and activation
of this lymphocyte subset under normal conditions. The second is to
fully explore the role of B cell-mediated immunity invoked after
influenza infection. The third is to reveal the means by which chronic
abuse of alcohol leads to compromised B lymphocyte function and poor
antibody responses in alcoholic patients.
B cell maturation and germinal center reactions: It is understood that B cells mature in the bone marrow and undergo a
well-defined developmental sequence. This process leads to a variety of
mature B cell subsets in the peripheral lymphoid organs (spleen and
lymph nodes) including follicular B cells, marginal zone B cells and B1 B
cells. The Waldschmidt laboratory has participated in a number of
studies to not only help clarify the various stages of B cell
development, but the factors necessary for maturation. Additional work
has focused on defining B cell subsets in the periphery as well as their
role in antibody-based immunity. Equally important, the laboratory is
interested in revealing key signals necessary for activation and
differentiation of mature B cells, especially those leading to germinal
centers (GCs), a key response that generates high affinity plasma cells
and memory B cells. These cell types produce antibodies crucial for
clearing the offending pathogen and protecting the host upon secondary
infection. Research is focused on understanding the complex cellular and
molecular events that occur within GCs, as well as the role T
regulatory cells play in governing this reaction.
B cell responses to infection with influenza virus: After primary infection with influenza virus (e.g. H1N1), cytotoxic CD8+
T cells play a central role in clearing the infection. However, B cells
are also activated and GCs induced in order to generate plasma and
memory cells that can produce anti-influenza antibodies. These
antibodies are crucial to prevent infection upon subsequent exposure to
the same virus, and can offer cross-protection to related viruses. The
induction of GCs and generation of antibodies is also the goal of
influenza vaccines, and the primary reason why these vaccines are
effective. The Waldschmidt laboratory is investigating the means by
which GCs are induced and regulated after influenza infection, not only
in the secondary lymphoid organs, but in the lungs as well. These
studies include exploring the role of both innate immunity and T
follicular helper cells in the induction and maintenance of
influenza-specific GCs.
Immune deficiency induced by chronic alcohol exposure:
Chronic alcohol consumption severely compromises the immune system
leading to a marked increase in infectious diseases. In collaboration
with a number of investigators within the Department, a mouse model of
long-term ethanol intake was established which recapitulates the immune
deficiency observed in humans. Using this model, the Waldschmidt
laboratory is focused on documenting lesions within the B cell
compartment, and the ethanol-induced events which lead to these defects.
Recent efforts have also led to the development of a fetal alcohol
exposure model, with offspring likewise exhibiting profound immune
deficiency.
(See complete publications list at PubMed)